Although training of respiratory muscles is a modality of therapy used to improve respiratory muscle function in patients with chronic lung disease, a number of important conceptual and practical questions regarding training and its effects on respiratory muscles remain to be solved. Using a chronically instrumented sheep preparation in which we have previously examined the response of the respiratory system to acutely imposed inspiratory flow resistive loads, we now propose to study the effect of training on the structure, enzymatic profiles and function of the diaphragm, intercostal, abdominal and genioglossus muscles. We will determine endurance time, tension-time index (transdiaphragmatic pressure x duty cycle) and the relation of those to ventilation, ventilatory timing, respiratory muscle EMG, 02 consumption of respiratory muscles and arterial blood gas tensions. We will examine also the effect of training on 1) muscle fiber types, capillary density, mitochrondrial number, volume and protein and the metabolic changes within the fiber types; 2) glycogen metabolism and glycolysis, activation and transfer of fatty acids into mitochondria, O2 of lipids, enzymes of the TCA cycle and respiratory chain; 3) muscle cell injury after inspiratory flow resistive loads of various durations and intensities as reflected in the formation of hyaline fibers, split fibers and necrosis. Because patients who might be considered for training are chronically hypoxemic, we also propose to study the effect of hypoxia on structure, metabolism and function of respiratory muscles. The physiologic measurements (Pdi, EMG, airflow, respiratory timing, 02 consumption, lung volume) are made using state of the art techniques and computerized methods. Histochemical, microscopic (light and electron) and photometric techniques will be used to assess the effect of training on structural changes in the respiratory muscles. The biochemical methods used for the determination of key enzymes are all operative in our laboratories. Although this proposal outlines a basic (biochemical and morphologic) approach in the study of respiratory muscle function before and after training, the integrative design of this proposal will very likely generate information that should be applicable to clinical practice.